Certain drugs and other agents are known to be capable of being topically administered to the skin to produce a local or systemic effect upon absorption into the skin. (As used herein, the term "agent" is employed in its broadest sense and applies to any drug or other substance which is delivered to the body to produce a desired, usually beneficial, effect on the recipient.) Originally this was accomplished by application of creams, ointments, gels, solutions or suspensions of the agent in a suitable carrier. This mode of application did not permit precise control of the dose or rate of administration because the amount of agent applied and the surface area covered were highly variable. Accordingly, transdermal delivery devices which deliver known amounts of drug to controlled areas of skin were developed. Representative devices are shown in U.S. Pat. Nos. are 3,249,109, 3,598,122, 4,144,317, 4,201,211, 4,262,003, 4,307,717, and 4,379,454, for example, which patents are incorporated herein by reference. The simplest type of a transdermal delivery device is an agent reservoir of predetermined size and composition, usually a matrix material containing dissolved or dispersed agent, maintained on a predetermined area of the skin for a predetermined period of time by adhesive or other means. Such matrix systems have the advantage of being easily fabricated and are generally of lower cost than more sophisticated rate controlled systems, although the rate of release of an agent from a simple matrix tends to decrease as a function of the time of use.
The site of administration of transdermal delivery devices have been selected at various locations such as behind the ear, on the chest or on the thigh for various reasons such as desired skin permeability to an agent, convenience or cosmetic reasons. It has been known for some time that permeability of human skin varies from site to site and that for certain agents scrotal skin tends to have a higher permability than other skin. Prior to our invention however the only means by which agents were administered through intact scrotal skin was by application of an ointment, cream, gel or solution of the agent and we were unaware of any delivery device suitable for transcrotal drug delivery. This was because the shape, texture, environment and sensitivity of the scrotum presented a combination of conditions which were incompatible with the application of prior art delivery devices and the maintenance of such a device in place for an extended time period without discomfort or other adverse side effects.
For example, we have found that the shape and texture of scrotal skin requires a highly flexible device possessing a certain amount of compliance or non-elastic stretch in order to be capable of comfortably conforming to the wrinkles, folds and irregular shape of scrotal skin in agent transmitting relationship thereto and thereafter remain in this slightly deformed condition rather than returning to its original configuration. Patient discomfort is a crucial factor in patient compliance and we have found that comfort depends not only on flexibility and stretchability but also on the texture of the device and the sensations attendant to removal. Typical contact adhesives, belts, buckles and elastic bands were all found to be unacceptably uncomfortable.
According to our invention we have devised a transdermal delivery device which is particularly adapted for the topical and systemic administration of agents to the skin at sensitive body sites such as the scrotum, labia, penis or underside of the breast, for example, for which heretofore there have been no suitable agent delivery platforms. Typical agents, by way of non-limiting examples, include androgens such as testosterone, estrogens such as estradiol, progestins such a progesterone, steroids such as hydrocortisone and cyproterone, peptides such as LHRH and interferon, and antiviral agents such as acyclovir and phenolphthalein. As used herein, the identification of an agent to be delivered includes not only the compound per se but also its topically administrable prodrugs, active metabolites and prodrugs of the active metabolites. Thus for example the reference to testosterone includes testosterone per se, its prodrugs such as testosterone enanthate, its active metabolite, dihydrotestosterone and its prodrug dihydrotestosterone enanthate, for example.
According to an embodiment of this invention, agent release through the body distal surface of this device is substantially reduced without adversely affecting the texture, flexibility, stretchability or tack.
Accordingly, it is an object of this invention to provide an agent delivery device particularly adapted for scrotal delivery of drugs and other agents through intact scrotal skin.
It is another object of this invention to provide a platform for agent delivery suitable for use on sensitive body sites such as the scrotum, labia, penis and breast.
It is another object of this invention to provide a simple, inexpensive transdermal agent delivery device particularly suited for delivering agents through sensitive body surfaces.
It is another object of this invention to deliver testosterone to a hypogonadal patient in a manner which produces blood levels which simulate normal daily blood level fluctuations.
It is another object of this invention to treat sexual dysfunction by transcrotal delivery of testosterone to obtain both a physiological and a psychological effect.